Salivary microbiome responses to chlorhexidine and Coriandrum sativum essential oil mouthwashes in patients with periodontitis in a randomized 2-week clinical trial

To compare the short-term salivary microbiome effects of a Coriandrum sativum essential oil (CSEO) mouthwash, chlorhexidine (CHX) as a benchmark comparator, and water in patients with periodontitis. In this randomized three-arm trial, participants with periodontitis rinsed twice daily for 14 days with water, CSEO, or 0.12% CHX. Preclinical anti- Porphyromonas gingivalis and fibroblast cytotoxicity assays informed CSEO concentration selection. Shotgun metagenomic sequencing was performed on 54 saliva libraries, two per participant, from 27 participants sampled at baseline and week 2 (H 2 O n = 9, CSEO n = 8, CHX n = 10). Alpha diversity, within-subject Bray-Curtis change, and differential abundance were analysed longitudinally. Both active agents inhibited P. gingivalis in vitro , with CHX showing greater potency. In the clinical trial, no statistically detectable difference between CSEO and water was observed for the primary species-level Bray-Curtis outcome (q = 0.413), alpha diversity (all q ≥ 0.259), or differential abundance. CHX showed greater species-level Bray-Curtis change than water (q = 0.020), lower species-level Simpson diversity (q = 0.014), and broad taxonomic restructuring. Under the tested formulation and exposure conditions, CSEO did not produce a statistically detectable group-level salivary microbiome shift relative to water. CHX provided a benchmark for broad ecological perturbation. The CSEO null finding does not exclude modest or heterogeneous effects in a larger cohort. No clinical benefit can be inferred from the absence of a detectable CSEO-associated microbiome shift. Larger studies integrating clinical, inflammatory, and direct functional outcomes are needed. ISRCTN79156900, retrospectively registered on 11 May 2026.